The present invention relates to a rapid nasal assay kit, which can determine the cause of nasal secretions. For a general review of rhinitis, its diagnoses and treatment, reference is made to M. Dykewicz, et al. Diagnoses and Management of Rhinitis: Complete Guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology, 81 Ann Allergy Asthma Immunol 478-518 (1998), incorporated herein by reference in its entirety.
Definition
Rhinitis is defined as a disorder characterized by a one or more of the following nasal symptoms: nasal congestion, rhinorrhea, sneezing, itching of the nose and/or post nasal drainage.
Classification
Rhinitis is classified by etiology as allergic or non allergic. Allergic rhinitis can be seasonal, perennial, episodic or occupational. Non allergic rhinitis can be infectious, perennial (or vasomotor rhinitis), NARES (non allergic rhinitis with eosinophilia syndrome), reflex induced (such as chemical), occupational or caused by atrophy, hormones, exercise or medication induced.
Prevalence
Chronic rhinitis symptoms are among the most common problems presenting to a physician. It has been estimated that 20 percent of the U.S. population has allergic rhinitis, or approximately 58 million people. Population survey results have estimated that 19 million Americans suffer from non allergic rhinitis.
Allergic Rhinitis
The symptoms of allergic rhinitis are often mediated by an IgE-mast cell-Th2 lymphocyte immune response. Allergic or atopic individuals respond to specific antigens according to the following mechanism: the antigen is processed by an antigen presenting cell (APC) and delivered to CD4+lymphocytes that release interleukin (IL)3, IL4, IL-5, and granulocyte macrophage colony stimulating factor (GMCSF) and other cytokines. These promote IgE production against these allergens by plasma cells, mast cell proliferation and infiltration of airway mucosa and eosinophilia.
An early phase for immediate allergic response may occur. IgE coated mast cells move into the epithelium, recognize mucosally-deposited allergen, and degranulate. Mast cell products include preformed mediators such as histamine, tryptase (a mast cell specific marker), chymase, kininogenase, heparin and other enzymes. ProstaglandinD2, and the cysteinyl-leukotrienes LTC4, LTD4 and LTE4 are also released. These mediators stimulate the vessels to leak and produce edema plus watery rhinorrhea, and dilate arteriole venule anastomoses causing nasal congestion. Release of these mast cell mediators and induction of these reactions occur within minutes and are termed the immediate or early allergic response.
A latent phase response is characterized primarily of nasal congestion. The mast cell mediators, including the cytokines, are thought to act upon post capillary endothelial cells to promote VCAM and E-selectin expression that permits lymphocytes to stick to the endothelial cells. Chemoattractants, such as IL-5 for eosinophils, promote the infiltration of the superficial lamina propria of the mucosa with some neutrophils and basophils, many eosinophils, and at a later time, T-lymphocytes and macrophages. Over the course of 4 to 8 hours these cells become activated and release their mediators, which activate many proinflammatory reactions of the immediate phase. Eosinophil products such as major basic protein, eosinophil cation protein, hypochlorate, leukotrienes and others are thought to damage the epithelium and other cells, inflammatory response that promotes the tissue damage of chronic allergic conditions.
TH2 lymphocytes are thought to play a critical role in promoting the allergic response by releasing their combination of IL-3, IL-4 and IL-5 and other cytokines that promotes IGE production, eosinophil chemoattraction and survival in tissues, and mast cell recruitment. The cytokines released from the TH2 lymphocytes, mast cells, eosinophils, basopbils and epithelial cells may circulate and cause fatigue, malaise, irritability and neurocognitive deficits that commonly affect those suffering from allergic rhinitis.
Non Allergic Rhinitis
When allergic causes of rhinitis have been excluded as the cause of rhinitis, a number of nasal conditions of partly unknown etiology and pathophysiology remains. This category is known as non allergic rhinitis and includes infectious rhinitis, hormonal rhinitis, vasomotor rhinitis, non allergic rhinitis with eosinophilia syndrome (NARES), certain types of occupational rhinitis and gustatory and drug induced rhinitis.
NARES is characterized by nasal congestion and prominent nasal eosinophilia. Neutrophilia infiltrates are usually seen with infectious rhinitis. LTB4, IL-7, bacterial products and complement fragments may activate neutrophils. The neutrophils may be seen in viral rhinitis syndromes as well. In addition, an increase in TH1 lymphocytes is indicative of non-allergic rhinitis. Other forms of non allergic rhinitis can be accounted for by hormonal changes, drug induced or idiopathic causes.
Diagnosis
Technically the diagnosis of allergic rhinitis is made by history, physical exam and specific IgE testing. The history focuses on allergic triggers, history of other associated allergic symptoms, past treatment experience and family history of allergies. The typical physical examination of the nasal mucosa reveals a pale and swollen mucosa with a blue gray appearance. Nasal secretions are typically watery and nasal congestion is common.
The demonstration of specific IgE antibodies to known allergens by skin testing or in vitro tests is important in determining whether the patient has allergic rhinitis. The other tests that help diagnose allergic rhinitis include anterior rhinoscopy, nasal endoscopy and imaging techniques such as a CAT scan, MRI or plain film radiographs to rule out associated sinusitis. Occasionally acoustic rhinomanometry is used to aerodynamically measure airway resistance. Nasal provocation tests using an allergen to determine whether an allergic reaction is produced, is unusual. Sometimes provocation testing with histamine or methacholine can be used to differentiate allergic from non allergic rhinitis, but there is frequent overlap between these conditions. Nasal cytology may aid in differentiating allergic rhinitis and NARES from other forms of non allergic rhinitis. Unproven forms of testing include cytotoxic testing, provocative and neutralization testing and measurement of specific and nonspecific IgG4.
Importance of Differentiating Allergic from Non Allergic Rhinitis
The first essential step in the treatment of rhinitis is to properly classify whether the patient has allergic or nonallergic rhinitis, since there is a fundamental difference in therapy. Allergic rhinitics are best treated with systemic antihistamines and mast cell stabilizers, and should avoid hyperosmolar saline sprays which can aggravate allergic symptoms. Conversely, nonallergic rhinitics should begin therapy with systemic decongestants, mucolytics and topical saline nasal sprays, and should strictly avoid antihistamines and mast cell stabilizers. The incorrect treatment of either condition leads to prolonged local and systemic symptoms and may even resulting complications such as acute or chronic sinusitis. With recent conversion of most antihistamines and decongestants to over-the-counter status, there is an increasing chance that the public will unknowingly take the wrong medicines. Similarly, if the public could rapidly diagnose the proper form of rhinitis, they can promptly and properly institute treatment, which would lead to significant cost savings by taking less medication, having fewer doctor visits and avoiding the progression to other complicated conditions such chronic sinusitis. Similarly, the health care professional treating a patient with a chronic or recurrent sinus or nasal condition is also often perplexed as to the exact etiology of the condition and treats the patient empirically, to see “how the patient responds” to a given form of therapy. If the patient does not respond favorably to a given therapy, other forms of therapy are given until the patient improves or requires referral to a specialist. This imposes and added burden on the patient with regard to time, cost and quality of life. The invention is also applicable to health care professionals that treat patients with sinus or nasal symptoms of disease.
Sinusitis is often a complication of chronic rhinitis and affects approximately 16 percent of the U.S. population, or about 32 million people. Chronic sinusitis accounts for about 11.7 million doctor visits annually. In 1996, overall health care expenditures attributable to chronic sinusitis in the U.S. were estimated to be over $5.8 billion. People suffering from chronic sinusitis miss an average of 4 days of work each year. A significant percent of chronic sinusitis results from nasal allergies that produce nasal edema and occlusion of the ostia of the sinuses. The treatment of sinusitis requires short-term and sometimes long-term antibiotic use as well as topical or oral steroid preparations and others.
Treatment
In general, most patients with allergic or non allergic rhinitis can be treated by over the counter medications, thanks in large part to the recent change in status of several popular prescription antihistamines and mucolytic/decongestants. The treatment of allergic rhinitis requires an oral antihistamine which blocks the action of histamine, and sometimes a mast cell stabilizer. Several non drowsy antihistamines are now available over the counter and include Claritin® and Allergra®. The mast cell stabilizer, cromolyn sodium, has been available over the counter for years. The treatment of non allergic rhinitis is with a mucolytic/decongestant often with saline nasal spray. In non allergic rhinitis, antihistamines are to be strictly avoided, especially with infectious rhinitis, as they may immediately worsen the symptom complex and rapidly lead to acute sinusitis. Topical nasal steroids which are still available by prescription only are useful in the treatment of both types of rhinitis.
What is needed is a rapid method of accurately determining which form or forms of rhinitis are present to help guide the patient to rapid, successful therapy.